Mixed Findings In Vitamin D Supplement Studies

The controversy over whether people should be supplementing with vitamin D or not, and whether there are health benefits or harms from vitamin D supplementation is heating up. While observational studies have found health benefits with higher vitamin D blood levels, the beneficial results have generally not held up (or mixed findings) when people were randomly assigned to groups (randomized clinical trials). Most agree that blood levels of under 20 ng per mL is too low, but an issue is what is a desirable blood level? Should healthy people routinely supplement?

Having higher blood levels of vitamin D from sunshine appears to be good (it's the sunshine vitamin, after all). It's the taking of a vitamin D supplement that is now controversial and being debated. By the way, if one decides to take a vitamin D supplement, then the D3 form is desirable (rather than D2).

It was pointed out that a number of negative health effects can occur in those taking more than 4000 IU daily of vitamin D. For example, it may cause toxic effects such as renal impairment, hypercalcemia, or vascular calcification. In 2014, 3% of all U.S. adults and 6.6% of adults older than 60 years reported taking a vitamin D supplement of 4,000 or more IU per day. [See all vitamin D posts - most discuss observational studies finding benefits.]

The following are articles from Medscape (the medical site) and American Family Physician discussing recent research that is not finding health benefits with vitamin D supplementation, or mixed findings (e.g. one review found it may be protective in lowering death from any reason or from cancer; also reduce the number of upper respiratory infections). Therefore, some medical groups suggest that vitamin D screening is an unnecessary test, a waste of money, and shouldn't be routinely done in healthy individuals. Note that many, many trials are going on right now to try to settle the vitamin D supplement issue (whether there are health benefits or not).

An updated literature review found no new evidence that vitamin D supplementation has an effect on most non-skeletal conditions, though it suggests there could be protective effects on all-cause and cancer-related deaths.

In their previous review on the health effects of vitamin D, Dr. Philippe Autier from the International Prevention Research Institute in Lyon, France, and colleagues evaluated relevant data published through the end of 2012, including seven meta-analyses and 88 trials not included in meta-analyses. That review found no evidence of a protective effect of vitamin D on non-skeletal conditions.

Their updated review, online October 25 in The Lancet Diabetes & Endocrinology, included 28 new meta-analyses and 100 trials published between 2013 and 2017 and came to similar conclusions. However, the researchers say, the more recent meta-analyses support earlier findings that 10 to 20 micrograms daily of vitamin D can reduce death from any cause and death from cancer in middle-aged and older adults.

“The meta-analyses included in this review that had different article selection and subgroup analyses continue to support the finding of a longer life expectancy after ordinary doses of vitamin D (20-30 micrograms/day) are given to middle-aged and older people, mainly when they are in hospital or living in an institution,” they write. They note that the 6% reduction in all-cause mortality found with vitamin D3 supplementation is in a similar range as the 9% mortality reduction seen in meta-analyses of statin trials.

And while vitamin D doses were higher than those assessed in the past, they found no new evidence that supplementation could have an effect on most non-skeletal conditions, including cardiovascular disease, adiposity, glucose metabolism, mood disorders, muscular function, tuberculosis, and colorectal adenomas, or on maternal and perinatal conditions. There wasn't much new data on cancer outcomes, they say, and no strong evidence to suggest an effect of vitamin D supplementation on biomarkers of systemic inflammation.

“The main new finding highlighted by this systematic review is that vitamin D supplementation might help to prevent common upper respiratory tract infections and asthma exacerbations,” the authors report. It's possible, they say, that vitamin D supplementation may exert immunomodulatory effects that strengthen resistance to acute infections. “The results of meta-analyses and trials in people with low 25(OH)D concentrations at baselinedo not support the hypothesis that vitamin D supplementation has a greater effect in these individuals,” they point out.

Recent trends in vitamin D testing and supplementation strongly suggest that physicians and patients believe that identifying and correcting vitamin D deficiency improves health outcomes. From 2000 to 2010, the volume of serum 25-hydroxyvitamin D (25-OH-D) tests reimbursed by Medicare Part B increased 83-fold.[1]In 2000, four out of 1,000 U.S. adults 70 years or older reported taking a daily vitamin D supplement of at least 1,000 IU, compared with four out of 10 in 2014—a 100-fold increase.

In contrast, LeFevre and LeFevre's review of the evidence for vitamin D screening and supplementation in adults in this issue of American Family Physician determined that these commonplace practices have virtually no established health benefits. The American Society for Clinical Pathology recommends against screening for vitamin D deficiency in the general population. The U.S. Preventive Services Task Force found insufficient evidence that vitamin D supplementation prevents cardiovascular disease, cancer, or fractures in community-dwelling adults.An umbrella review of more than 100 systematic reviews and meta-analyses of observational studies and randomized controlled trials found only a handful of "probable" relationships between serum vitamin D concentrations and clinical outcomes, and concluded that vitamin D supplementation does not increase bone mineral density or reduce the risk of fractures or falls in older adults.

Screening for vitamin D deficiency leads to hundreds of millions of dollars wasted in testing costs annually.Low-level daily supplementation with calcium and vitamin D can increase the risk of kidney stones, and higher monthly doses of vitamin D increased the risk of falls in a randomized controlled trial of older adults with vitamin D deficiency. The National Academy of Medicine has noted that vitamin D intakes above the tolerable upper limit of 4,000 IU per day may cause toxic effects such as renal impairment, hypercalcemia, or vascular calcification. In 2014, 3% of all U.S. adults and 6.6% of adults older than 60 years reported taking a vitamin D supplement of 4,000 or more IU per day.

Family physicians should also counsel patients on the recommended dietary allowance for vitamin D (600 IU per day in adults 70 years and younger, and 800 IU per day in adults older than 70 years), and discourage most patients from using supplements, especially in dosages near or above the tolerable upper limit of 4,000 IU per day.

Measurement of vitamin D levels and supplementation with oral vitamin D have become commonplace, although clinical trials have not demonstrated health benefits. The usefulness of serum 25-hydroxyvitamin D levels to assess adequate exposure to vitamin D is hampered by variations in measurement technique and precision. Serum levels less than 12 ng per mL reflect inadequate vitamin D intake for bone health. Levels greater than 20 ng per mL are adequate for 97.5% of the population. Routine vitamin D supplementationdoes not prolong life, decrease the incidence of cancer or cardiovascular disease, or decrease fracture rates. Screening asymptomatic individuals for vitamin D deficiency and treating those considered to be deficient do not reduce the risk of cancer, type 2 diabetes mellitus, or death in community-dwelling adults, or fractures in persons not at high risk of fractures. Randomized controlled trials of vitamin D supplementation in the treatment of depression, fatigue, osteoarthritis, and chronic pain show no benefit, even in persons with low levels at baseline.